Education and Training
Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells
Patients with hematologic malignancies will receive myeloablative chemotherapy followed by stem cell rescue with bone marrow or hematopoietic peripheral blood stem cells collected by apheresis from a filgrastim- (G-CSF)-mobilized haploidentical related-donor, ie, hematopoietic peripheral blood stem cell transplant (HSCT).
Stanford is currently not accepting patients for this trial.
Intervention(s):
- drug: Regulatory T-cells
- drug: Conventional T-cells
- drug: Melphalan
- drug: Thiotepa
- device: Fludarabine
- drug: Anti-thymocyte globulin, rabbit
- drug: CliniMACS CD34 Reagent System
Eligibility
Inclusion Criteria
RECIPIENT
- Histopathologically-confirmed:
- Acute leukemia (in first remission with poor risk factors and molecular prognosis)
- Acute myelogenous leukemia (AML) with -5,-7, t (6;9), tri8, -11
- Acute lymphoblastic leukemia (ALL) with Ph+ t (9;22), t (4;22), (q34;q11)
- Acute leukemia with refractory disease or > Complete Remission (CR) 1
- Chronic myelogenous leukemia (CML) (accelerated, blast or second chronic phase)
- Myelodysplastic syndrome (in high and high intermediate risk categories)
- Non-Hodgkin's lymphoma (NHL) with poor risk features and not suitable for autologous
transplantation
- Refractory Chronic lymphocytic leukemia (CLL)
- At least 21 days from the end of most recent prior therapy to start of the transplant
conditioning regimen
- Must be < 60 years old at time of registration.
- Karnofsky Performance Status (KPS) > 70%
Must have related donor who is:
- Genotypically human leukocyte antigen (HLA) -A, B,C and DR beta 1 (DRB1), DQ loci
haploidentical to the recipient (but differing for 2 to 3 HLA alleles on the unshared
haplotype in the graft-versus-host disease (GvHD) direction)
- No HLA-matched sibling or matched-unrelated donor is identified.
- Adequate cardiac and pulmonary function (left ventricular ejection fraction (LVEF) >
45%, diffusing capacity of the lungs for carbon monoxide (DLCO) >50% corrected for
hemoglobin)
- Serum creatinine < 1.5 mg/dL OR Creatinine clearance > 50 mL/min for those above serum
creatinine at least 1.5 mg/dL
- Serum bilirubin < 2.0 mg/dL
- Alanine transaminase (ALT) < 2x upper normal limit (ULN) (unless secondary to disease)
- No prior myeloablative therapy or hematopoietic cell transplantation
DONOR:
- Age ≤ 70 years
- Weight ≥ 25 kg.
- Medical history and physical examination confirm good health status as defined by
institutional standards
- Seronegative for HIV Ag within 30 days of apheresis collection for:
- Hepatitis B surface antigen (sAg) or polymerase chain reaction (PCR) +
- Hepatitis C ab or PCR+
- Genotypically haploidentical as determined by HLA typing
- Female donors (child-bearing potential) must have a negative serum or urine beta-human
chorionic gonadotropin (HCG) test within 3 weeks of mobilization
- Capable of undergoing leukapheresis
- Has adequate venous access
- Willing to undergo insertion of a central catheter if leukapheresis via peripheral
vein is inadequate
- Capable of agreeing to second donation of peripheral blood progenitor cell (PBPC) (or
a bone marrow harvest) should the patient fail to demonstrate sustained engraftment
following the transplant
- Institutional review board (IRB)-approved consent form signed by donor or legal
guardian > 18 years of age
Donor Selection in the priority order:
- Recipient's biological mother preferred, if available
- Other available haploidentical donors will be selected based upon the presence of
natural killer (NK) alloreactivity between donor and recipient by high-resolution HLA
typing of the C locus. An NK-alloreactive donor will be preferentially chosen.
Recipients lacking a killer immunoglobulin-like receptor (KIR)-ligand present in the
donor along with the corresponding KIR defines "NK alloreactivity".
- If more than one NK-alloreactive donor is available, preference is to cytomegalovirus
(CMV)-seronegative donor
Exclusion Criteria
RECIPIENT:
- Suitable candidate for autologous transplantation or allogeneic transplantation with
an available matched-related or matched-unrelated donor
- Seropositive for:
- HIV ab
- Hepatitis B sAg or PCR+
- Hepatitis C ab or PCR+
- History of invasive Aspergillosis
- Any active, uncontrolled bacterial, viral or fungal infection
- Uncontrolled central nervous system (CNS) disease involvement
- Lactating female
DONOR:
- Evidence of active infection or viral hepatitis
- Factors of increased risk for complications from leukapheresis or granulocyte-colony
stimulating factor (G-CSF) therapy
- Lactating female
- HIV-positive
Ages Eligible for Study
N/A - 60 Years
Genders Eligible for Study
All
Not currently accepting new patients for this trial
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
ccto-office@stanford.edu
650-498-7061
Not Recruiting